Participants in organized sports-particularly football, hockey, and soccer-are at increased risk for sustaining one, and often multiple, concussions. Not only can multiple concussions cause long-term or permanent neurologic dysfunction, but there is evidence that athletes who suffer a second concussion before they have fully recovered from the first, are vulnerable to acute, severe brain swelling or death. However, there are no reliable standards for determining when an athlete can safely return to play after a concussion nor whether different criteria are needed depending on their age or gender. Such guidelines await elucidation of the pathophysiology and long-term effects of concussion, which are poorly understood. Current standards of care vary widely and are based on subjective experiences. They do not utilize physiological or neurocognitive measures. Two years ago, we developed a battery of neurocognitive tests (ImPACT) that assesses memory and attention, the two most common cognitive functions impaired by concussion. We have field tested ImPACT and found that this battery accurately reflects the onset and resolution of concussion-induced symptoms. During the next 5 years, we plan to use functional MRI (fMRI) to study 200 high school and college athletes who have suffered a concussion, in order to characterize post-concussive abnormalities in brain activation patterns. We will correlate changes in fMRI activation patterns with changes detected using a conventional test of working memory (N-Back), and also with the ImPACT battery. Using this paradigm, we will measure the effects of single vs. multiple concussions. The influences of age and gender on these abnormalities will be determined. Finally, we will assess how well changes in fMRI activation patterns, symptoms of concussion, and objective cognitive abnormalities correlate with each other and with academic performance 3 and 6 months after injury. We expect the results of this study to provide a physiologic and anatomic underpinning for the cognitive deficits observed after one or more concussions in different at-risk groups. Such information should enable the development of better guidelines for return to play, school, or work. The results of this study also will help determine which medications or other therapies are most likely to benefit victims of concussion in subsequent therapeutic trials.